Amyloid and the Brain: Alzheimer's Disease and Stroke

Health Professional

One of the very confusing and commonly misunderstood features of Alzheimer's disease is how we make the diagnosis. In previous blogs I have discussed this topic from what is typically called the top-down approach. The top-down approach is the typical clinical approach, the typical way health care professionals attempt to make a diagnosis of Alzheimer's disease. We take a history from and perform an examination of the patient and try to put this information together. When this is successful, there is a general sense of accomplishment, and for those of you who watched and remember the TV show the A Team, this making of the diagnosis is a little like the end of the show when Hannibal would say, "Isn't it nice when a plan comes together." That is what it is like for the health care people, as they make a diagnosis and presumably begin to understand the probable brain abnormalities affecting the patient.

There is an alternative way to understand the probable brain abnormalities in a disease. That is to determine the brain abnormalities directly and then correlate them with the clinical presentation (the history and physical examination). This might be called a bottom-up approach. For example, if someone has a skin problem that might be a skin cancer, the approach is to biopsy (make an incision and take a small piece of) the abnormality. By doing this, there is a direct assessment of the skin tissue and a direct understanding of what is wrong. For obvious reasons this cannot be the standard approach to a brain disease. Performing a biopsy of the brain is a process that involves too much risk.

However, if we could biopsy the brain of a patient with Alzheimer's disease, there are certain features we would look for. One of them is amyloid. For those of you who are chronic readers of this blog, you probably remember me touching previously on amyloid. Amyloid is a protein that collects in the brain tissue of patients with Alzheimer's disease, forming, among other things, plaques. Plaques are ball shaped objects that occur in the parts of the brain that are most affected by the disease. 100% of patients with Alzheimer's disease have amyloid plaques in their brains. Current attempts to treat Alzheimer's disease focus on blocking the formation of amyloid or eliminating it from the brain. Amyloid is also the target of some new tests, for example the use of Pittsburgh compound B, a test that I have discussed in a previous blog.

The above information is the information that is most often addressed in discussions about amyloid. However, there is an additional aspect of importance for amyloid in older patients, including patients with Alzheimer's disease. This is a problem called amyloid angiopathy. Amyloid angiopathy is a disorder that is characterized by amyloid collecting in the walls of blood vessels that are in the brain. These collections of amyloid weaken the blood vessel walls.   Weakness of the blood vessel walls can lead to rupture of the blood vessel wall and bleeding into the brain. If the amount of bleeding is sufficient, there may be neurological injury. Neurological injury from bleeding in the brain is stroke. In this setting we have a very interesting situation. If someone with Alzheimer's disease has bleeding into the brain causing a stroke, we can take the history and perform the physical examination and, using the top-down approach, conclude that the diagnosis is probable amyloid angiopathy. There is however, a method of making this diagnosis by the bottom-up approach. This disease may also cause small episodes of bleeding, typically in the back of the brain. If this happens, the patient's MRI will show small dark dots.   Therefore, looking at an MRI of the patient's brain, even without the patient being talked to or examined, allows us to make the diagnosis of amyloid angiopathy. Because of the possible strokes, the presence of amyloid angiopathy in a patient with Alzheimer's disease can be as devastating to the patient as the amyloid plaques.

What I hope I have shown in this discussion of amyloid, are two things. First, that it is possible for health care professionals to approach the diagnosis of a patient from more than one perspective. Again demonstrating why it is possible at times for different diagnostic conclusions to be reached. Second, I hope, that in the context of my previous blogs that have discussed amyloid, you may begin to appreciate the extraordinary complexity of Alzheimer's disease.